title: Sigma-1 receptor function is critical for both the discriminative stimulus and aversive effects of the kappa-opioid receptor agonist U-50488H.
abstract: The present study was undertaken to identify possible similarities between the effects of kappa-opioid receptor agonist, N-methyl-D-aspartate-receptor antagonist, and sigma receptor agonist on the discriminative stimulus effects of U-50488H, and the possible involvement of sigma receptors in the discriminative stimulus and aversive effects of U-50488H. The kappa-opioid receptor agonist U-50488H produced significant place aversion as measured by the conditioned place preference procedure, and this effect was completely abolished by treatment with the putative sigma-1 receptor antagonist NE-100. In addition, phencyclidine (+)-SKF-10047 and (+)-pentazocine, which are sigma receptor agonists, generalized to the discriminative stimulus effects of U-50488H in rats that had been trained to discriminate between U-50488H (3.0 mg/kg) and saline. Furthermore, NE-100 significantly attenuated the discriminative stimulus effects of U-50488H and the U-50488H-like discriminative stimulus effects of phencyclidine. These results suggest that the sigma-1 receptor is responsible for both the discriminative stimulus effects and aversive effects of U-50488H.
authors.affiliation: Hoshi University School of Pharmacy and Pharmaceutical Science, Japan Wakayama Medical University Hospital, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Mori
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Nomura
authors.forename: Kana
authors.initials: K
authors.lastname: Isotani
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Torigoe
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Tsukiyama
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*; D000097605:Sigma-1 Receptor
chemical_list: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000840:Anisoles; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D010423:Pentazocine; D010620:Phenazocine; D010622:Phencyclidine; D011437:Propylamines; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C012134:SK&F 10047